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http://dx.doi.org/10.15616/BSL.2021.27.4.223

Glutamine Inhibits TNF-α-induced Cytosolic Phospholipase A2 Activation via Upregulation of MAPK Phosphatase-1  

Yoon, So Young (Department of Biological Sciences, College of Natural Sciences, Chonnam National University)
Jeong, Soo-Yeon (Department of Biological Sciences, College of Natural Sciences, Chonnam National University)
Im, Suhn-Young (Department of Biological Sciences, College of Natural Sciences, Chonnam National University)
Publication Information
Biomedical Science Letters / v.27, no.4, 2021 , pp. 223-230 More about this Journal
Abstract
Tumor necrosis factor alpha (TNF-α) is a principal regulator of inflammation and immunity. The proinflammatory properties of TNF-α can be attributed to its ability to activate the enzyme cytosolic phospholipase A2 (cPLA2), which generates potent inflammatory lipid mediators, eicosanoids. L-glutamine (Gln) plays physiologically important roles in various metabolic processes. We have reported that Gln has a potent anti-inflammatory activity via rapid upregulation of mitogen-activated protein kinases (MAPKs) phosphatase (MKP)-1, which preferentially dephosphorylates the key proinflammatory enzymes, p38 MAPK and cytosolic phospholipase A2 (cPLA2). In this study, we have investigated whether Gln could inhibit TNF-α-induced cPLA2 activation. Gln inhibited TNF-α-induced increases in cPLA2 phosphorylation in the lungs and blood levels of the cPLA2 metabolites, leukotrine B4 (LTB4) (lipoxygenase metabolite) and prostaglandin E2 (PGE2) (cyclooxygenase metabolite). TNF-α increased p38 and cPLA2 phosphorylation and blood levels of LTB4 and PGE2, which were blocked by the p38 inhibitor SB202190. Gln inhibited TNF-α-induced p38 and cPLA2 phosphorylation and production of the cPLA2 metabolites. Such inhibitory activity of Gln was no longer observed in MKP-1 small interfering RNA-pretreated animals. Our data indicate that Gln inhibited TNF-α-induced cPLA2 phosphorylation through MKP-1 induction/p38 inhibition, and suggest that the utility of Gln in inflammatory diseases in which TNF-α plays a major role in their pathogenesis.
Keywords
Glutamine; TNF-${\alpha}$; $cPLA_2$; p38 MAPK; MKP-1;
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